XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation

Sun, JianminLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Ningxia Medical University (author)

In order to investigate the molecular mechanisms by which the oncogenic mutant KIT/D816V causes transformation of cells, we investigated proteins that selectively bind KIT/D816V, but not wild-type KIT, as potential mediators of transformation. By mass spectrometry several proteins were identified, among them a previously uncharacterized protein denoted XKR5 (XK-related protein 5), which is related to the X Kell blood group proteins. We could demonstrate that interaction between XKR5 and KIT/D816V leads to phosphorylation of XKR5 at Tyr 369, Tyr487, and Tyr 543. Tyrosine phosphorylated XKR5 acts as a negative regulator of KIT signaling, which leads to downregulation of phosphorylation of ERK, AKT, and p38. This led to reduced proliferation and colony forming capacity in semi-solid medium. Taken together, our data demonstrate that XKR5 is a novel type of negative regulator of KIT-mediated transformation.

Thingholm, TineLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,University of Southern Denmark(Swepub:lu)med-ttm (author)
Højrup, PeterUniversity of Southern Denmark (author)
Rönnstrand, LarsLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Skåne University Hospital(Swepub:lu)klke-lro (author)
Avdelningen för translationell cancerforskningInstitutionen för laboratoriemedicin (creator_code:org_t)

By the author/editor: Sun, Jianmin; Thingholm, Tine; Højrup, Peter; Rönnstrand, Lars

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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